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PubMed2004

A comparison of lung function methods for assessing dose-response effects of salbutamol.

Pulmonary function methods which are able to detect small pharmacological effects may be useful for assessing the full dose-response curve of bronchodilatators. We compared the ability of impulse oscillometry (R5, R20, X5, RF), plethysmography (sGaw) and spirometry [forced expiratory volume in 1 s (FEV(1)), maximal mid expiratory flow rate (MMEF)] to measure the dose-response effects of salbutamol in 12 healthy subjects, 12 mild asthmatics (mean FEV(1) 96% predicted) and 12 moderate asthmatics (mean FEV(1) 63% predicted). The techniques were performed twice to assess variability. Then salbutamol 10, 20, 100, 200 and 800 microg was administered. The sensitivity of the methods were compared by determining the lowest dose that caused changes greater than variability. In healthy subjects significant changes (p < or = 0.05) were observed only in FEV(1) (4.1%) and MMEF (14.6%) at 100 microg and sGaw (25.6%) and R20 (8.3%) at 200 microg. In mild asthmatics significant changes were observed in sGaw (15.9%) at 10 microg, X5 (23%), RF (20.3%) and MMEF (15.7%) at 20 microg, R5 (13.9%) and R20 (9.4%) at 100 microg and FEV(1) (7.1%) at 200 microg. All measurements except R20 demonstrated significant changes at 10 micro g in moderate asthmatics. The most sensitive test for assessing bronchodilatation is different in healthy subjects and asthmatics, and varies with severity of airflow obstruction.

Adult↗
PubMed2004

Comparison of bronchoprotective and bronchodilator effects of a single dose of formoterol delivered by hydrofluoroalkane and chlorofluorocarbon aerosols and dry powder in a double blind, placebo-controlled, crossover study.

BACKGROUND: In response to the phasing out of chlorofluorocarbon (CFC) inhalers, a metered dose hydrofluoroalkane (HFA) formulation, Modulite (Chiesi Farmaceutici S.p.A, Parma, Italy), to be delivered with a pressurized metered dose inhaler (pMDI), has been developed. Modulite is a HFA formulation technology that has been designed to provide stable and uniform dose delivery of HFA-based formulations to enable an easy transition from CFC to HFA inhalers. OBJECTIVES: The aim of this study was to compare the bronchoprotective and bronchodilator effects of a single dose of 12 microg of formoterol from the HFA Modulite inhaler with the Foradil Aerolizer (dry powder inhaler, DPI) and the Foradil CFC inhalers (Novartis Health Consumer, Basel, Switzerland). METHODS: This was a double blind, double dummy, randomized, placebo-controlled, crossover study conducted in 38 subjects with mild to moderate asthma (mean forced expiratory volume in 1 s [FEV1] 87.5% predicted). The primary endpoint was methacholine challenge provocative dose required for 20% fall in the FEV1 (PD20) 90 min post dose. Bronchodilation was assessed with spirometry (FEV1, FVC, FEF25-75) and impulse oscillometry (resistance at 5 and 20 Hz, reactance at 5 Hz and resonant frequency) over the 90 min post dose. In a subset of 12 subjects formoterol plasma levels, serum potassium and glucose were determined up to 480 min post dose. RESULTS: The three formoterol formulations demonstrated significant (P < or = 0.05) improvements in bronchoprotection compared to placebo and non-inferiority of the HFA preparation compared to the CFC and DPI preparations was demonstrated. Geometric mean PD20 values were 0.51 mg with HFA, 0.62 mg with DPI, 0.62 mg with CFC and 0.2 mg with placebo. The log transformed mean differences in PD20 doubling dose between HFA and (a) DPI was -0.28 (95% CI -0.84-0.29, P = 0.57) (b) CFC was -0.28 (95% CI -0.84-0.28, P = 0.57) and (c) placebo was 1.38 (95% CI 0.82-1.94, P < 0.001). Serum potassium, glucose and formoterol plasma profiles were comparable for the CFC, HFA and DPI devices. CONCLUSION: Our findings of similar efficacy, pharmacokinetics and systemic effects of the HFA formoterol inhaler compared to the CFC and DPI preparations supports the potential use of this novel formulation in the treatment of asthma.

Administration, Inhalation↗
PubMed1977

Late voice function after surgical injury to the recurrent nerve.

In the period 1960 to 1970, a total of 213 patients underwent subtotal thyroidectomy for benign cervical toxic goitre. Postoperatively, immobile vocal cord indicating paralysis of the recurrent nerve was found in 17 patients. In 8 patients, immobility of the vocal cord was permanent. Seven of the 17 patients received voice training which was initiated within 3 weeks after operation. After a period of 5-10 years, on an average 8 years, the 17 patients had a clinical and a comprehensive objective examination of the voice function comprising stroboscopy, electroglottography, phono-oscillometry, voice range, phonation time, peak-flow and pitch. Only a few complaints were ciliated whereas the objective examination of the voice function revealed abnormal findings in all but one patient. The findings were less abnormal in patients who had received early voice training. It is concluded that despite abnormal objective findings, all 17 patients found their voice function satisfactory. Moreover, early voice training seemed to offer a fair chance of minimizing late voice problems, whether the paralysis was permanent or transitory.

Adult↗
PubMed1995

Pulmonary sympathetic denervation does not increase airway resistance in patients with chronic obstructive pulmonary disease (COPD).

Whether or not neural blockade of pulmonary sympathetic innervation is of relevance for airway resistance in patients with chronic obstructive pulmonary disease (COPD) is unknown. Accordingly we evaluated airway resistance during sympathetic blockade by high thoracic epidural anaesthesia in patients with COPD. Before and 45 min after thoracic epidural injection of bupivacaine 0.75% (6-8 ml; n = 10) total respiratory resistance (oscillometry, ROS), vital capacity (VC), forced expiratory vital capacity in 1 s (FEV1, [%VC]), functional residual capacity (FRC; helium dilution method), and arterial blood gases were measured. Three additional patients received bupivacaine intravenously (1.2 mg.min-1 for 45 min), another three received saline epidurally. Sensory blockade covered segment C5 through T8. As an indicator of widespread sympathetic blockade including the lungs, skin temperature increased significantly on thumb and little toe. Despite pulmonary sympathetic denervation ROS, FEV1, and FRC remained unchanged, while VC decreased slightly, probably due to intercostal muscle blockade. Blood gases remained constant. Neither intravenous bupivacaine nor epidural saline evoked directional changes. Since, in contrast to beta-adrenoceptor blockade, pulmonary sympathetic denervation did not increase airway resistance in patients with COPD, neural sympathetic blockade seems to be of no relevance for airway resistance in these patients.

Airway Resistance↗
PubMed1992

Correlation between computer-assisted femoral arteriography and physiological tests in hypercholesterolaemic patients: a methodological study with special reference to clinical trials.

The validity of computer-assisted femoral arteriography, for the study of regression/progression of atherosclerosis in follow-up clinical trials, was investigated by comparison with routine physiological estimates of peripheral circulatory function. Thus, in 114 hypercholesterolaemic patients, the results of aorto-femoral arteriography were compared with those of leg segmental blood pressure measurement, oscillometry, digital pulse plethysmography, and bicycle and treadmill exercise tests. In 107 patients, 18 with symptoms of peripheral vascular disease (PVD) and 89 asymptomatic, magnification arteriograms of a 20 cm segment of the right or left superficial femoral artery were obtained. These arteriograms were digitized and the following variables were calculated: arterial lumen volume (corrected for body size), per cent stenosis, and edge roughness. The correlation between arteriographic and physiological variables was investigated with a linear regression model, taking into account the possible interaction with sex, and presence or absence of symptoms of PVD. Lumen volume correlated significantly with all five physiological variables, and per cent stenosis correlated significantly with four of the physiological variables. For the roughness measure, however a significant correlation was found only with plethysmography. By using logistic multiple regression analysis linear functions of physiological variables were constructed to detect ilio-femoral arterial occlusion. The sensitivity/specificity for detection of right-sided, left-sided, and bilateral occlusion was 0.83/0.98, 0.78/0.98, and 0.60/1.00 respectively (N = 108-111). Systolic blood pressure (ankle-arm ratio) was the single variable most closely correlated to the likelihood of arterial occlusions. It is concluded that arterial lumen volume and per cent stenosis, measured for the digitized femoral arteriogram, correlate well with physiological variables, which reflect the state of atherosclerosis both in the femoral arteries and in other arterial beds including the heart, and that routine physiological tests can be used to identify patients with arterial occlusions in the iliac and femoral arteries.

Adult↗
PubMed1993

Non-invasive estimates of aortic root pressures: external subclavian arterial pulse tracing calibrated by oscillometrically determined brachial arterial pressures.

This investigation assessed the ability of a non-invasive method to reproduce aortic root pressure waveform and pressures. An external pulse tracing of the subclavian artery was obtained simultaneously with direct aortic root pressures during routine left heart catheterization in 26 patients (aged 39-74 years) with various cardiovascular disorders. Indirect brachial arterial peak-systolic and nadir-diastolic pressures were obtained with oscillometry. The direct and indirect peak-systolic and nadir-diastolic pressures, were separately used to calibrate the pulse tracing. Adequate pulse tracing was obtained in 19 patients (73%). The waveforms agreed well with cross-correlation coefficients for systole and diastole of 0.98. The difference between the pulse trace and the direct pressure curve, when the first was calibrated with the peak-systolic and nadir-diastolic pressures of the latter on average was less than 1 mmHg for systole and diastole. At end-systole the mean difference was 5 mmHg. Oscillometric brachial arterial peak-systolic pressures were (mean +/- SD) 3 +/- 7 mmHg below the corresponding direct measurements, while diastolic pressures were 8 +/- 4 mmHg above. The difference between the pulse trace and the direct pressure curve, when the pulse trace was calibrated with oscillometric pressures, was at end-systole 6 +/- 6 mmHg and for mean arterial pressures 5 +/- 4 mmHg. Thus, the external subclavian arterial pulse tracing provides a non-invasive, clinically feasible access to the aortic root pressure waveform. With optimal calibration, good estimates of aortic root pressures throughout systole and diastole can be obtained, while end-systolic pressure tends to be slightly overestimated.

Adult↗
PubMedDate not supplied

Gender differences in vascular compliance in young, healthy subjects assessed by pulse contour analysis.

OBJECTIVES: Sex hormones exert important effects on the vasculature. Female sex hormones have been reported to enhance endothelial function, reduce oxidative stress, and protect against atherosclerosis. However, the effects of estrogen on vascular compliance have not been studied. Recently, noninvasive instrumentation that estimates vascular compliance by recording the radial artery pulse contour has been introduced. Reductions in the oscillatory or reflected component of the diastolic waveform have been observed in various clinical conditions, including hypertension, diabetes mellitus, and congestive heart failure, and may reflect endothelial dysfunction at the site of resistance vessels. In this study the authors examined gender-related vascular compliance in a cohort of young, healthy, predominantly nonsmoking, medication-free men and women to determine the influence of cardiovascular risk factors, including family and social history, serum lipids, plasma homocysteine, and insulin levels on vascular compliance. METHODS: The volunteers, consisting of 151 healthy men and women (mean age 24A+/-4 years) completed a questionnaire detailing family and social history, medication use, and exercise habits. Large (C1) and small (C2) vessel compliance and various cardiovascular parameters were derived from arterial pulse wave contour analysis. Systolic, diastolic, and mean arterial blood pressure, pulse pressure, and pulse rate were determined simultaneously by oscillometry. Blood for fasting serum lipids, plasma homocysteine, and serum insulin were obtained in a subset of 135 subjects. RESULTS: The questionnaire revealed that 38% of parents had a history of hypertension, 31% had dyslipidemia, and 15% had coronary heart disease. C2 was lower in subjects with parental dyslipidemia. Compared to men, women had lower C2; lower systolic blood pressure, mean arterial pressure, and pulse pressure; higher serum high-density lipoprotein cholesterol; lower serum triglycerides; and lower plasma homocysteine, but similar serum insulin levels. C1 correlated with height and pulse pressure, whereas C2 was proportional to height and weight and inversely related to systemic vascular resistance. Multivariate regression analysis showed that stroke volume, total vascular impedance, cardiac output, female gender, and systemic vascular resistance independently predicted changes in C2, but that height was not a significant factor. CONCLUSIONS: Women have reduced C2 despite lower systolic blood pressure and pulse pressure and more favorable lipid and homocysteine levels. C2 is independent of height and is lower in subjects with parental dyslipidemia. These data indicate that female sex hormones have unexpected negative effects on small vessel compliance. They may help to explain why premenopausal women hospitalized for myocardial infarction have higher mortality rates than men of the same age.

Adolescent↗
PubMed2006

Blood pressure components in clinical hypertension.

This review offers a critical evaluation of the remarkable progress in antihypertensive therapy since its inception. Despite the introduction of newer, more sophisticated drugs, treatment results have remained stable. Problems impeding further improvement include limited patient compliance, clinical inertia, incomplete adherence to guidelines, and dependence on brachial artery cuff pressures for diagnosis, risk assessment, and treatment response. Brachial artery systolic and pulse pressures do not reliably represent aortic or carotid artery pressures, which are better risk predictors for the heart and brain. Mean pressure, which is the same throughout the arterial tree, is directly measurable by cuff oscillometry, and might become the best single risk predictor. Available drugs have limited ability to decrease the aortic stiffness that is responsible for the elevated systolic blood pressure of aging. Therefore, to improve risk assessment and therapeutic benefit, we might include mean blood pressure and pulse pressure into blood pressure measurements, pursue efforts to measure central blood pressure, and search for new drugs to reduce arterial stiffness.

Antihypertensive Agents↗
PubMed1988

The prevalence and one-year outcome of limb arterial obstructive disease in a nursing home population.

To assess the utility of bedside diagnostic measures to detect prognostically significant peripheral vascular disease, we examined 60 nursing home residents by physical examination, Doppler sphygmomamometry and pneumatic oscillometry, and recorded the clinical history. Eighty-eight percent of the cases had tibial/brachial arterial systolic pressure indices below 0.95, the lower limit traditionally considered normal. Yet, no more than 5% of the patients carried a previous diagnosis of peripheral vascular disease or had intermittent claudication, leg ulcers or gangrene. Approximately half of the patients had tibial/brachial pressure indices less than 0.7, and one year later in these cases, there was significantly greater morbidity and nearly twice the mortality of patients with less severe disease. We conclude that simple bedside diagnostic tests of arterial disease used in this study discloses a high prevalence of disease in institutionalized elderly patients and identifies a group at particular risk for morbid complications.

Aged↗
PubMed1996

The influence of some perinatal variables on neonatal blood pressure.

Adult hypertension has been linked to fetal growth. This study investigates whether this link is evident in the newborn. We measured blood pressure by oscillometry in 248 healthy neonates on day 3/4 of life. Antenatal data and neonatal measurements were obtained from hospital records. Elevated neonatal blood pressure correlated with higher birthweight. There was no correlation between placental weight and blood pressure. Babies born by caesarean section had lower systolic blood pressure. Babies of maternal smokers had higher diastolic blood pressure, but their mothers (45% of this study) had lower blood pressure than non-smokers. Thus, smoking was associated with a significant change in both maternal and neonatal blood pressure, and may be an important influence on the developing cardiovascular system.

Analysis of Variance↗
PubMed2003

Exhaled nitric oxide rather than lung function distinguishes preschool children with probable asthma.

BACKGROUND: Respiratory function and airway inflammation can be evaluated in preschool children with special techniques, but their relative power in identifying young children with asthma has not been studied. This study was undertaken to compare the value of exhaled nitric oxide (FE(NO)), baseline lung function, and bronchodilator responsiveness in identifying children with newly detected probable asthma. METHODS: Ninety six preschool children (age 3.8-7.5 years) with asthmatic symptoms or history and 62 age matched healthy non-atopic controls were studied. FE(NO) was measured with the standard online single exhalation technique, and baseline lung function and bronchodilator responsiveness were measured using impulse oscillometry (IOS). RESULTS: Children with probable asthma (n=21), characterised by recent recurrent wheeze, had a significantly higher mean (SE) concentration of FE(NO) than controls (22.1 (3.4) ppb v 5.3 (0.4) ppb; mean difference 16.8 ppb, 95% CI 12.0 to 21.5) and also had higher baseline respiratory resistance, lower reactance, and larger bronchodilator responses expressed as the change in resistance after inhalation of salbutamol. Children with chronic cough only (n=46) also had significantly raised mean FE(NO) (9.2 (1.5) ppb; mean difference 3.9 ppb, 95% CI 0.8 to 7.0) but their lung function was not significantly reduced. Children on inhaled steroids due to previously diagnosed asthma (n=29) differed from the controls only in their baseline lung function. The analysis of receiver operating characteristics (ROC) showed that FE(NO) provided the best power for discriminating between children with probable asthma and healthy controls, with a sensitivity of 86% and specificity of 92% at the cut off level of 1.5 SD above predicted. CONCLUSIONS: FE(NO) is superior to baseline respiratory function and bronchodilator responsiveness in identifying preschool children with probable asthma. The results emphasise the presence of airway inflammation in the early stages of asthma, even in young children.

Airway Resistance↗
PubMed1999

beta-2 Adrenergic receptor variants affect resting blood pressure and agonist-induced vasodilation in young adult Caucasians.

Recent evidence suggests that the prodownregulatory Gly16 allele of the beta-2 adrenergic receptor (beta-2 AR) is associated with essential hypertension in African Caribbeans. To further investigate the effect of the glycine (Gly)16 and arginine (Arg)16 beta-2 AR variants on hemodynamics, we investigated the agonist-mediated in vivo vasodilation in normotensive Austrian Caucasians and analyzed the results with respect to the Gly16/Arg16 polymorphism. Fifty-seven normotensive men, 20 to 32 years of age with body mass index of 18.7 to 29.9 kg/m2, were genotyped for the Arg16/Gly16 beta-2 AR alleles. All 15 Gly16/Gly16 subjects, all 12 Arg16/Arg/16 subjects, and 27 of 30 heterozygous subjects underwent hemodynamic measurements while supine after an overnight fast. The observers were unaware of the subjects' genotypes. The subjects received a graded infusion of the selective beta-2 AR agonist salbutamol (0.07, 0.14, and 0.21 microgram/kg per minute, respectively), each dose over 8 minutes. Stroke volume and blood pressure were determined continuously by means of impedance cardiography and oscillometry, respectively. The last 4 minutes of each infusion were evaluated statistically. Basal mean blood pressure was higher in the Gly16/Gly16 subjects compared with Arg16/Arg16 subjects (mean+/-SD: 81.6+/-6.14 versus 75.2+/-4.93 mm Hg, P<0.01). Homozygous Gly16 subjects showed a significantly decreased vasodilation during the first dose of salbutamol infusion compared with Arg16/Arg16 subjects (Deltatotal peripheral resistance index -17.9+/-14.4 versus -30. 6+/-8.3%, P<0.01) despite increased sympathetic counterregulation in the Arg16/Arg16 group (Deltaheart rate +16.9+/-7.0% versus +8.6+/-7. 0%, P<0.01; Deltacardiac index +39.5+/-18.5% versus 21.4+/-18.8%, P<0.05). Our results provide additional evidence that the Gly16/Arg16 alleles of the beta-2 AR are intimately related to blood pressure regulation and deserve further studies in the pathogenesis of essential hypertension.

Adrenergic beta-Agonists↗
PubMed2001

Function of pulmonary neuronal M(2) muscarinic receptors in stable chronic obstructive pulmonary disease.

Anticholinergic drugs often cause a considerable degree of bronchodilation in patients with chronic obstructive pulmonary disease (COPD). Pulmonary neuronal M(2) muscarinic receptors function to limit the magnitude of vagally induced bronchoconstriction. We hypothesized that the effectiveness of anticholinergic agents in patients with COPD may reflect increased vagal reactivity due to dysfunction of M(2) muscarinic receptors. The function of M(2) receptors and the magnitude of vagally induced bronchoconstriction were assessed in subjects with normal lung function and in subjects with COPD. A nasal cold dry air challenge was used to induce a bronchoconstriction, measured as a change in airway resistance (Raw) at 5 Hz (R5) using impulse oscillometry. In subjects with COPD R5 rose from 0.68 +/- 0.06 to 0.74 +/- 0.07 kPa/L/s after the cold dry air challenge (p < 0.01) and in the control subjects R5 rose from 0.34 +/- 0.03 to 0.39 +/- 0.03 kPa/L/s (p < 0.01). The bronchoconstriction was inhibited by pretreatment with ipratropium bromide, indicating that it was vagally mediated. In both groups of subjects pretreatment with the selective M(2) muscarinic receptor agonist pilocarpine (5 mg/ml) prevented the cold air-induced bronchoconstriction, indicating normal function of M(2) receptors. These studies indicate that M(2) muscarinic receptors are functional in subjects with stable COPD.

Aged↗
PubMed2002

Efficiency of cold passover and heated humidification under continuous positive airway pressure.

Cold passover and heated humidifiers are employed for the prevention of side-effects associated with continuous positive airway pressure (CPAP) treatment. However, to date, it has not been possible to separately measure the humidity of inspired and expired air. The aim of this study was to compare the relative humidity of the inspired air and the water loss during respiration between cold passover and heated humidifiers under CPAP. Humidity and temperature were determined separately for the respiratory phases, without humidification, with cold passover and heated humidifiers in 10 healthy subjects. Humidity was measured with a capacitive hygrometer, temperature with a "Type K" thermosensor, and impedance of the total respiratory system with impulse oscillometry. The relative humidity (rH) of the inspired air (mean+/-SD) increased significantly from 24.0+/-9.1%, rH (34.8+/-1.0 degrees C, no humidifier) to 34.5+/-10.1%, rH (34.6+/-1.0 degrees C) under cold humidification, and to 53.9+/-13.2% rH (35.0+/-1.1 degrees C) under heated humidification. With heated humidification, water loss was reduced by 38% compared to cold humidification. The impedance increased from 5.7+/-1.8 cmH2O x L x s(-1) (no humidifier) to 6.7+/-1.8 cmH2O x L x s(-1) (heated humidifier). The authors conclude that the use of a heated humidifier during continuous positive airway pressure appreciably increases the relative humidity of the inspired air and reduces the water loss during respiration.

Adolescent↗
PubMed2006

Early low cardiac output is associated with compromised electroencephalographic activity in very preterm infants.

Low cerebral blood flow in preterm infants has been associated with discontinuous electroencephalography (EEG) activity that in turn has been associated with poor long-term prognosis. We examined the relationships between echocardiographic measurements of blood flow, blood pressure (BP), and quantitative EEG data as surrogate markers of cerebral perfusion and function with 112 sets of paired data obtained over the first 48 h after birth in 40 preterm infants (24-30 wk of gestation, 510-1900 g at delivery). Echocardiographic measurements of right ventricular output (RVO) and superior vena caval (SVC) flow were performed serially. BP recordings were obtained from invasive monitoring or oscillometry. Modified cotside EEGs were analyzed for quantitative amplitude and continuity measurements. RVO 12 h after birth was related to both EEG amplitude at 12 and 24 h and continuity at 24 h. Mean systemic arterial pressure (MAP) at 12 and 24 h was related to continuity at 12 and 24 h after birth. Multiple regression analyses revealed that RVO at 12 h was related to median EEG amplitude at 24 h and diastolic BP at 24 h was related to simultaneous EEG continuity. In addition, at 12 h, infants in the lowest quartile for RVO measurements (<282 mL/kg/min) had lower EEG amplitude and those in the lowest quartile for MAP measurements (<31 mm Hg) had lower EEG continuity. These results suggest a relationship between indirect measurements of cerebral perfusion and cerebral function soon after birth in preterm infants.

Animals↗
PubMed2024

Design of the SPIROMICS Study of Early COPD Progression: SOURCE Study.

BACKGROUND: The biological mechanisms leading some tobacco-exposed individuals to develop early-stage chronic obstructive pulmonary disease (COPD) are poorly understood. This knowledge gap hampers development of disease-modifying agents for this prevalent condition. OBJECTIVES: Accordingly, with National Heart, Lung and Blood Institute support, we initiated the SubPopulations and InteRmediate Outcome Measures In COPD Study (SPIROMICS) Study of Early COPD Progression (SOURCE), a multicenter observational cohort study of younger individuals with a history of cigarette smoking and thus at-risk for, or with, early-stage COPD. Our overall objectives are to identify those who will develop COPD earlier in life, characterize them thoroughly, and by contrasting them to those not developing COPD, define mechanisms of disease progression. METHODS/DISCUSSION: SOURCE utilizes the established SPIROMICS clinical network. Its goal is to enroll n=649 participants, ages 30-55 years, all races/ethnicities, with &#x2265;10 pack-years cigarette smoking, in either Global initiative for chronic Obstructive Lung Disease (GOLD) groups 0-2 or with preserved ratio-impaired spirometry; and an additional n=40 never-smoker controls. Participants undergo baseline and 3-year follow-up visits, each including high-resolution computed tomography, respiratory oscillometry and spirometry (pre- and postbronchodilator administration), exhaled breath condensate (baseline only), and extensive biospecimen collection, including sputum induction. Symptoms, interim health care utilization, and exacerbations are captured every 6 months via follow-up phone calls. An embedded bronchoscopy substudy involving n=100 participants (including all never-smokers) will allow collection of lower airway samples for genetic, epigenetic, genomic, immunological, microbiome, mucin analyses, and basal cell culture. CONCLUSION: SOURCE should provide novel insights into the natural history of lung disease in younger individuals with a smoking history, and its biological basis.

SPIROMICS↗
PubMed1988

The hypotensive mechanism of percutaneous transluminal dilatation (PTD) in renovascular hypertension due to bilateral renal artery stenosis.

The hypotensive mechanism of percutaneous transluminal dilatation (PTD) in renovascular hypertension due to bilateral renal artery was investigated in two patients. Blood pressure was monitored continuously before, during and after PTD by use of a new automated blood pressure monitoring device based on finger volume-oscillometry. Plasma renin activity was measured repeatedly before, during and after PTD. A hypotensive effect appeared immediately after PTD and blood pressure remained low in the following observation period without any hypotensive medication. In these cases, the hypotension was accompanied by a transient decrease in heart rate immediately after PTD. The hypotensive response to PTD was not parallel to the basal plasma renin activity, suggesting that the renin-angiotensin system is not necessarily involved in the maintenance of the hypertension before PTD. The autonomic nervous system seemed to play a certain role. Since the hypotension was accompanied by a transient decrease in heart rate immediately after PTD, the hypotension may be induced either by a decrease in sympathetic tone or by an increase in vagal tone at least just after PTD. It is hypothesized that these changes in autonomic nervous activity are mediated centrally through the renal afferent mechanism in response to rapid changes in renal hemodynamics induced by PTD.

Adult↗
PubMed2003

Increased serum IGF-I during pregnancy is associated with progression of diabetic retinopathy.

The IGF system has been associated with development and progression of diabetic retinopathy. We examined whether a simple measurement of the IGF system (serum total IGF-I) correlated with progression of diabetic retinopathy in pregnancy in type 1 diabetes. A prospective observational study was performed in 103 pregnant women with type 1 diabetes. Serum IGF-I was measured in maternal serum from week 14, every fourth week until week 30, and every second week until delivery. Twenty-four-hour blood pressure was measured with a portable oscillometry monitor. The women had visual acuity testing and fundus photography before pregnancy, once in each trimester, and 4 months after birth. Each eye was assigned an overall retinopathy grade on a scale from 1 to 6 independently by two experienced graders. During pregnancy, serum IGF-I increased with increasing gestational age until a plateau was reached in week 32. Progression of retinopathy was significantly associated with a higher level of IGF-I (P < 0.01). Serum IGF-I increased with increasing progression of retinopathy. Change of retinopathy was significantly associated with level of IGF-I (P < 0.01). During pregnancy, serum IGF-I increased with increasing birth weight until a plateau was reached in week 32. Birth weight was significantly associated with a higher level of serum IGF-I (P < 0.01).

Adult↗